Pyridin-2-ylmethylsulphinyl-1H-benzimidazoles and compounds of a closely related structure, as known, for example, from EP-A-0005129, EP-A-0166287, EP-A-0174726 and EP-A-0268956, are, owing to their H+/K+-ATPase-inhibitory action, of considerable importance in the therapy of diseases associated with an increased secretion of gastric acid.
Examples of active compounds from this class of compounds which are commercially available or in clinical development are 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methylsulphinyl]-1H-benzimidazole (INN: omeprazole), (S)-5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl-sulphinyl]-1H-benzimidazole (INN: esomeprazole), 5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridinyl)methylsulphinyl]-1H-benzimidazole (INN: pantoprazole), 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl)methylsulphinyl]-1H-benzimidazole (INN: Iansoprazole), 2-{[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulphinyl}-1H-benzimidazole (INN: rabeprazole) and 5-methoxy-2-((4-methoxy-3,5-dimethyl-2-pyridylmethyl)sulphinyl)-1H-imidazo[4,5-b)pyridine (INN: tenatoprazole).
The abovementioned sulphinyl derivatives which, owing to their mechanism of action, are also referred, to as proton pump inhibitors or abbreviated PPI are chiral compounds. The process usually used for preparing the PPI is the oxidation of the corresponding sulphides. This oxidation gives—unless particular measures are taken—a racemic mixture comprising about the same proportions of the two enantiomers (stereoisomers), i.e. the (+)- and (−)-form or the (R)- and (S)-form of the PPI.
Since enantiomers are thermally relatively stable, i.e. they do not racemize on storage—in particular in solid form—there has in the past been no lack of efforts to separate PPI enantiomer mixtures or to prepare the PPI enantiomers in more or less pure form.